tbuckley/cabot-search huggingface dataset:
Comparison of 18F-FDG and 68Ga-FAPI PET/CT in a Rare Renal Leiomyoma
Authors: Yanggang Liu, Shumao Zhang, Lianjun Lan, Yue Chen, Lin Qiu
Journal: Clinical Nuclear Medicine (2023)

Abstract Renal leiomyoma is a rare benign mesenchymal tumor of the kidney, which mainly originates from the renal capsule or pelvis. We described 18 F-FDG and 68 Ga-FAPI PET/CT findings in a case of renal leiomyoma. The PET/CT findings showed that the left renal leiomyoma demonstrated intensively increased 68 Ga-FAPI uptake, whereas only inhomogeneously slightly increased 18 F-FDG uptake. This case illustrates that 68 Ga-FAPI PET/CT may be an effective tool for detecting renal leiomyoma.
Interplay of Mendelian and polygenic risk factors in Arab breast cancer patients
Authors: Mohammed Al-Jumaan, Hoyin Chu, Abdullah Alsulaiman, Sabrina Y. Camp, Seunghun Han, Riaz Gillani, Yousef Al Marzooq, Fatmah Almulhim, Chittibabu Vatte, Areej Al Nemer, Afnan Almuhanna, Eliezer M. Van Allen, Amein Al-Ali, Saud H. AlDubayan
Journal: Genome Medicine (2023)

Abstract Background Breast cancer patients from the indigenous Arab population present much earlier than patients from Western countries and have traditionally been underrepresented in cancer genomics studies. The contribution of polygenic and Mendelian risk toward the earlier onset of breast cancer in the population remains elusive. Methods We performed low-pass whole genome sequencing (lpWGS) and whole-exome sequencing (WES) from 220 female breast cancer patients unselected for positive family history from the indigenous Arab population. Using publicly available resources, we imputed population-specific variants and calculated breast cancer burden-sensitive polygenic risk scores (PRS). Variant pathogenicity was also evaluated on exome variants with high coverage. Results Variants imputed from lpWGS showed high concordance with paired exome (median dosage correlation: 0.9459, Interquartile range: 0.9410–0.9490). After adjusting the PRS to the Arab population, we found significant associations between PRS performance in risk prediction and first-degree relative breast cancer history prediction (Spearman rho=0.43, p = 0.03), where breast cancer patients in the top PRS decile are 5.53 (95% CI 1.76–17.97, p = 0.003) times more likely also to have a first-degree relative diagnosed with breast cancer compared to those in the middle deciles. In addition, we found evidence for the genetic liability threshold model of breast cancer where among patients with a family history of breast cancer, pathogenic rare variant carriers had significantly lower PRS than non-carriers ( p = 0.0205, Mann-Whitney U test) while for non-carriers every standard deviation increase in PRS corresponded to 4.52 years (95% CI 8.88–0.17, p = 0.042) earlier age of presentation. Conclusions Overall, our study provides a framework to assess polygenic risk in an understudied population using lpWGS and identifies common variant risk as a factor independent of pathogenic variant carrier status for earlier age of onset of breast cancer among indigenous Arab breast cancer patients.
A Mitochondria‐Targeted Ferroptosis Inducer Activated by Glutathione‐Responsive Imaging and Depletion for Triple Negative Breast Cancer Theranostics (Adv. Healthcare Mater. 22/2023)
Authors: Hongbo Gan, Xie Huang, Xi Luo, Jinlin Li, Banghui Mo, Lizhi Cheng, Qiuxia Shu, Zaizhi Du, Hong Tang, Wei Sun, Liting Wang, Shenglin Luo, Songtao Yu
Journal: Advanced Healthcare Materials (2023)

Theranostics Recent evidence indicates that mitochondria play a crucial role in ferroptosis-induced cell death. In article 2300220 by Shenglin Luo, Songtao Yu, and co-workers, a mitochondria-targeted ferroptosis inducer (IR780-SPhF) is successfully designed for triple negative breast cancer imaging and therapy. It can exhibit preferential accumulation in cancer cell mitochondria and efficient glutathione depletion, remarkably boosting ferroptosis-mediated cell death and glutathione-responsive turn-on fluorescence emission.
Facile Synthesis of Highly Stretchable, Tough, and Photodegradable Hydrogels (Adv. Healthcare Mater. 22/2023)
Authors: Rita G. Fonseca, Aline Kuster, Pedro P. Fernandes, Mahmoud Tavakoli, Patrícia Pereira, José R. Fernandes, Francesco De Bon, Arménio C. Serra, Ana C. Fonseca, Jorge F. J. Coelho
Journal: Advanced Healthcare Materials (2023)

Biosensors In article 2300918 by Ana C. Fonseca, Jorge F. J. Coelho, and co-workers, a simple method for preparing highly stretchable, tough, and photodegradable double-network hydrogels using ortho-nitrobenzyl (ONB) crosslinkers with different poly(ethylene glycol) sizes is reported. The stringent design of ONB structures enables the control of degradation time. The properties of these hydrogels pave the way for a new generation of environmentally friendly substrates that can be used for bioelectronics.
High‐Throughput Bioprinting of Geometrically‐Controlled Pre‐Vascularized Injectable Microgels for Accelerated Tissue Regeneration (Adv. Healthcare Mater. 22/2023)
Authors: Cristiane M. Franca, Avathamsa Athirasala, Ramesh Subbiah, Anthony Tahayeri, Prakash Selvakumar, Amin Mansoorifar, Sivaporn Horsophonphong, Ashley Sercia, Lina Nih, Luiz E. Bertassoni
Journal: Advanced Healthcare Materials (2023)

Tissue Engineering Article 2202840 by Luiz E. Bertassoni and co-workers presents a bioprinting strategy for high-throughput and scalable manufacturing of geometrically controlled injectable microgels, which are loaded with built-in vascular capillaries. Microgels are prevascularized through assembly of encapsulated endothelial and mesenchymal stem cells into pericyte supported capillaries, which are demonstrated to allow for rapid anastomosis of engineered human vessels with the host vasculature for accelerated tissue regeneration.
4D Printing of Personalized‐Tunable Biomimetic Periosteum with Anisotropic Microstructure for Accelerated Vascularization and Bone Healing (Adv. Healthcare Mater. 22/2023)
Authors: Chao Liu, Yiting Lou, Zheyuan Sun, Haiying Ma, Mouyuan Sun, Shengjie Li, Dongqi You, Junjie Wu, Binbin Ying, Wanghui Ding, Mengfei Yu, Huiming Wang
Journal: Advanced Healthcare Materials (2023)

4D Printing In article 2202868 by Binbin Ying, Wanghui Ding, Mengfei Yu, and co-workers, the process of bone defect repair mediated by biomimetic periosteum is vividly conveyed through the famous Chinese folk story “The Coilang and the Weaver Meet on the Bridge”. The constructed biomimetic periosteum through ultraviolet light-based micropattern printing contains biophysical signals and spatially adjustable properties, which is expected to orchestrate an optimal microenvironment for bone regeneration. The biomimetic periosteum (the bridge in the cartoon) provides a channel for host osteoblasts (the Coilang in the cartoon) and stem cells (the Weaver in the cartoon) to migrate rapidly (the birds and the lantern) to the bone defect area and recruits various growth factors. This work provides a novel route to actively facilitate local angiogenesis and early-stage osteogenesis in the bone defect area (clouds on either side).
Wnt3a‐Loaded Hydroxyapatite Nanowire@Mesoporous Silica Core−Shell Nanocomposite Promotes the Regeneration of Dentin−Pulp Complex via Angiogenesis, Oxidative Stress Resistance, and Odontogenic Induction of Stem Cells (Adv. Healthcare Mater. 22/2023)
Authors: Nan Luo, Yu‐Wei Deng, Jin Wen, Xiao‐Chen Xu, Rui‐Xue Jiang, Jing‐Yu Zhan, Yu Zhang, Bing‐Qiang Lu, Feng Chen, Xi Chen
Journal: Advanced Healthcare Materials (2023)

Tissue Regeneration In article 2300229 by Bing-Qiang Lu, Feng Chen, Xi Chen, and co-workers, a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica core-shell nanocomposite is developed for treatment of pulp exposure. This protein/ion delivery system effectively regulates biological behaviors of cells for dentin-pulp complex regeneration via angiogenesis, oxidative stress resistance and odontogenic induction.
Two-drug antiretroviral regimens for HIV
Authors: John P Thornhill, Ben Cromarty, Jessica Gaddie, Shiellah Mushunje, Rashida A Ferrand
Journal: BMJ (2023)

What you need to know".• Antiretroviral therapy regimens containing two active drugs rather than the traditional three or more are now shown to be efficacious in treating HIV.• Two-drug therapy is a particularly useful option when tenofovir alafenamide, tenofovir disoproxil fumarate or abacavir cannot be used or are not optimal such as in people with high cardiovascular risk, renal impairment or decreased bone mineral density.• Certain two-drug regimens are used in the setting of switching ART in people who already have an undetectable HIV viral load.• Two-drug therapy is not suitable for people with HIV and Hepatitis B co-infection or in those with a history of HIV drug resistance or during pregnancy.• Long-acting injectable two-drug therapy is also available, but this is not suitable in those with a high body mass index, certain viral subtypes, or in those with HIV drug resistance.
Widespread RNA-based cas regulation monitors crRNA abundance and anti-CRISPR proteins
Authors: Chao Liu, Rui Wang, Jie Li, Feiyue Cheng, Xian Shu, Huiwei Zhao, Qiong Xue, Haiying Yu, Aici Wu, Lingyun Wang, Sushu Hu, Yihan Zhang, Jun Yang, Hua Xiang, Ming Li
Journal: Cell Host & Microbe (2023)
Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease
Authors: Andy P. Tsai, Chuanpeng Dong, Peter Bor-Chian Lin, Adrian L. Oblak, Gonzalo Viana Di Prisco, Nian Wang, Nicole Hajicek, Adam J. Carr, Emma K. Lendy, Oliver Hahn, Micaiah Atkins, Aulden G. Foltz, Jheel Patel, Guixiang Xu, Miguel Moutinho, John Sondek, Qisheng Zhang, Andrew D. Mesecar, Yunlong Liu, Brady K. Atwood, Tony Wyss-Coray, Kwangsik Nho, Stephanie J. Bissel, Bruce T. Lamb, Gary E. Landreth
Journal: Immunity (2023)

Genetic association studies have demonstrated the critical involvement of the microglial immune response in Alzheimer's disease (AD) pathogenesis. Phospholipase C-gamma-2 (PLCG2) is selectively expressed by microglia and functions in many immune receptor signaling pathways. In AD, PLCG2 is induced uniquely in plaque-associated microglia. A genetic variant of PLCG2, PLCG2P522R, is a mild hypermorph that attenuates AD risk. Here, we identified a loss-of-function PLCG2 variant, PLCG2M28L, that confers an increased AD risk. PLCG2P522R attenuated disease in an amyloidogenic murine AD model, whereas PLCG2M28L exacerbated the plaque burden associated with altered phagocytosis and Aβ clearance. The variants bidirectionally modulated disease pathology by inducing distinct transcriptional programs that identified microglial subpopulations associated with protective or detrimental phenotypes. These findings identify PLCG2M28L as a potential AD risk variant and demonstrate that PLCG2 variants can differentially orchestrate microglial responses in AD pathogenesis that can be therapeutically targeted.
Optimization of Cas12a for multiplexed genome-scale transcriptional activation
Authors: Audrey L. Griffith, Fengyi Zheng, Abby V. McGee, Nathan W. Miller, Zsofia M. Szegletes, Ganna Reint, Fabian Gademann, Ifunanya Nwolah, Mudra Hegde, Yanjing V. Liu, Amy Goodale, John G. Doench
Journal: Cell Genomics (2023)

Cas12a CRISPR technology, unlike Cas9, allows for facile multiplexing of guide RNAs from a single transcript, simplifying combinatorial perturbations. While Cas12a has been implemented for multiplexed knockout genetic screens, it has yet to be optimized for CRISPR activation (CRISPRa) screens in human cells. Here, we develop a new Cas12a-based transactivation domain (TAD) recruitment system using the ALFA nanobody and demonstrate simultaneous activation of up to four genes. We screen a genome-wide library to identify modulators of growth and MEK inhibition, and we compare these results with those obtained with open reading frame (ORF) overexpression and Cas9-based CRISPRa. We find that the activity of multiplexed arrays is largely predictable from the best-performing guide and provide criteria for selecting active guides. We anticipate that these results will greatly accelerate the exploration of gene function and combinatorial phenotypes at scale.
High morbidity and mortality in children with untreated congenital deficiency of leptin or its receptor
Authors: Sadia Saeed, Roohia Khanam, Qasim M. Janjua, Jaida Manzoor, Lijiao Ning, Sharoon Hanook, Mickaël Canouil, Muhammad Ali, Hina Ayesha, Waqas I. Khan, I. Sadaf Farooqi, Giles S.H. Yeo, Stephen O'Rahilly, Amélie Bonnefond, Taeed A. Butt, Muhammad Arslan, Philippe Froguel
Journal: Cell Reports Medicine (2023)

The long-term clinical outcomes of severe obesity due to leptin signaling deficiency are unknown. We carry out a retrospective cross-sectional investigation of a large cohort of children with leptin (LEP), LEP receptor (LEPR), or melanocortin 4 receptor (MC4R) deficiency (n = 145) to evaluate the progression of the disease. The affected individuals undergo physical, clinical, and metabolic evaluations. We report a very high mortality in children with LEP (26%) or LEPR deficiency (9%), mainly due to severe pulmonary and gastrointestinal infections. In addition, 40% of surviving children with LEP or LEPR deficiency experience life-threatening episodes of lung or gastrointestinal infections. Although precision drugs are currently available for LEP and LEPR deficiencies, as yet, they are not accessible in Pakistan. An appreciation of the severe impact of LEP or LEPR deficiency on morbidity and early mortality, educational attainment, and the attendant stigmatization should spur efforts to deliver the available life-saving drugs to these children as a matter of urgency.
Active cortical networks promote shunting fast synaptic inhibition in vivo
Authors: Richard J. Burman, Paul J.N. Brodersen, Joseph V. Raimondo, Arjune Sen, Colin J. Akerman
Journal: Neuron (2023)

Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABAARs). Despite their fundamental role, it is still not known how GABAARs signal in the intact brain. Here, we use in vivo gramicidin recordings to investigate synaptic GABAAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients. In anesthetized cortex, synaptic GABAARs exert classic hyperpolarizing effects. In contrast, GABAAR-mediated synaptic signaling in awake cortex is found to be predominantly shunting. This is due to more depolarized GABAAR equilibrium potentials (EGABAAR), which are shown to result from the high levels of synaptic activity that characterize awake cortical networks. Synaptic EGABAAR observed in awake cortex facilitates the desynchronizing effects of inhibitory inputs upon local networks, which increases the flexibility of spiking responses to external inputs. Our findings therefore suggest that GABAAR signaling adapts to optimize cortical functions.
Differential cortical network engagement during states of un/consciousness in humans
Authors: Rina Zelmann, Angelique C. Paulk, Fangyun Tian, Gustavo A. Balanza Villegas, Jaquelin Dezha Peralta, Britni Crocker, G. Rees Cosgrove, R. Mark Richardson, Ziv M. Williams, Darin D. Dougherty, Patrick L. Purdon, Sydney S. Cash
Journal: Neuron (2023)
Deep learning analysis of blood flow sounds to detect arteriovenous fistula stenosis
Authors: George Zhou, Yunchan Chen, Candace Chien, Leslie Revatta, Jannatul Ferdous, Michelle Chen, Shourov Deb, Sol De Leon Cruz, Alan Wang, Benjamin Lee, Mert R. Sabuncu, William Browne, Herrick Wun, Bobak Mosadegh
Journal: npj Digital Medicine (2023)

Abstract For hemodialysis patients, arteriovenous fistula (AVF) patency determines whether adequate hemofiltration can be achieved, and directly influences clinical outcomes. Here, we report the development and performance of a deep learning model for automated AVF stenosis screening based on the sound of AVF blood flow using supervised learning with data validated by ultrasound. We demonstrate the importance of contextualizing the sound with location metadata as the characteristics of the blood flow sound varies significantly along the AVF. We found the best model to be a vision transformer trained on spectrogram images. Our model can screen for stenosis at a performance level comparable to that of a nephrologist performing a physical exam, but with the advantage of being automated and scalable. In a high-volume, resource-limited clinical setting, automated AVF stenosis screening can help ensure patient safety via early detection of at-risk vascular access, streamline the dialysis workflow, and serve as a patient-facing tool to allow for at-home, self-screening.
Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
Authors: Lina Guo, Jinsong Ding, Wenhu Zhou
Journal: Acta Pharmaceutica Sinica B (2023)

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate (CaCO3) biomineralized Salmonella (Sal) as an in-situ cancer vaccine producer and systematical ITM regulator. CaCO3 can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO3 shell was decomposed at an acidic microenvironment to attenuate tumor acidity, accompanied by the release of Sal and Ca2+/A23187. Specifically, Sal served as a cancer vaccine producer by inducing cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca2+, on the other hand, was internalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.
The value of Augmented Reality in surgery — A usability study on laparoscopic liver surgery
Authors: João Ramalhinho, Soojeong Yoo, Thomas Dowrick, Bongjin Koo, Murali Somasundaram, Kurinchi Gurusamy, David J. Hawkes, Brian Davidson, Ann Blandford, Matthew J. Clarkson
Journal: Medical Image Analysis (2023)

Augmented Reality (AR) is considered to be a promising technology for the guidance of laparoscopic liver surgery. By overlaying pre-operative 3D information of the liver and internal blood vessels on the laparoscopic view, surgeons can better understand the location of critical structures. In an effort to enable AR, several authors have focused on the development of methods to obtain an accurate alignment between the laparoscopic video image and the pre-operative 3D data of the liver, without assessing the benefit that the resulting overlay can provide during surgery. In this paper, we present a study that aims to assess quantitatively and qualitatively the value of an AR overlay in laparoscopic surgery during a simulated surgical task on a phantom setup. We design a study where participants are asked to physically localise pre-operative tumours in a liver phantom using three image guidance conditions - a baseline condition without any image guidance, a condition where the 3D surfaces of the liver are aligned to the video and displayed on a black background, and a condition where video see-through AR is displayed on the laparoscopic video. Using data collected from a cohort of 24 participants which include 12 surgeons, we observe that compared to the baseline, AR decreases the median localisation error of surgeons on non-peripheral targets from 25.8 mm to 9.2 mm. Using subjective feedback, we also identify that AR introduces usability improvements in the surgical task and increases the perceived confidence of the users. Between the two tested displays, the majority of participants preferred to use the AR overlay instead of navigated view of the 3D surfaces on a separate screen. We conclude that AR has the potential to improve performance and decision making in laparoscopic surgery, and that improvements in overlay alignment accuracy and depth perception should be pursued in the future.
A population-based study of transformed marginal zone lymphoma: identifying outcome-related characteristics
Authors: Johanna A. A. Bult, Francien Huisman, Yujie Zhong, Nick Veltmaat, Joost Kluiver, Sanne H. Tonino, Joost S. P. Vermaat, Martine E. D. Chamuleau, Arjan Diepstra, Anke van den Berg, Wouter J. Plattel, Mirian Brink, Marcel Nijland
Journal: Blood Cancer Journal (2023)

Abstract Histological transformation of marginal zone lymphoma (tMZL) into diffuse large B-cell lymphoma is associated with poor outcomes. Clinical characteristics associated with transformation risk and outcome after transformation are largely unknown due to scarcity of data. In this population-based study, competing risk analyses were performed to elucidate clinical characteristics associated with developing transformation among 1793 MZL patients using the Netherlands Cancer Registry. Cox regression analyses were performed to elucidate clinical characteristics associated with risk of relapse and mortality after transformation. Transformation occurred in 75 (4%) out of 1793 MZL patients. Elevated LDH and nodal MZL subtype at MZL diagnosis were associated with an increased risk, and radiotherapy with a reduced risk of developing tMZL. Most tMZL patients received R-(mini)CHOP ( n = 53, 71%). Age &gt;60 years and (immuno)chemotherapy before transformation were associated with an increased risk of relapse and mortality after transformation. Two-year progression-free survival (PFS) and overall survival (OS) were 66% (95% CI 52–77%) and 75% (95% CI 62–85%) for R-(mini)CHOP-treated tMZL patients, as compared to a PFS and OS both of 41% (95% CI 19–63%) for patients treated otherwise. Our study offers comprehensive insights into characteristics associated with transformation and survival after transformation, thereby optimizing guidelines and patient counseling.
Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application
Authors: Han Liu, Zhiyang Wen, Zihan Liu, Yanfang Yang, Hongliang Wang, Xuejun Xia, Jun Ye, Yuling Liu
Journal: Acta Pharmaceutica Sinica B (2023)

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability. Calcium-based materials can also deliver contrast agents, which can enhance real-time imaging and exert a Ca
A+T rich interaction domain protein 3a (Arid3a) impairs Mertk-mediated efferocytosis in cholestasis
Authors: Ruiling Chen, Bingyuan Huang, Min Lian, Yiran Wei, Qi Miao, Jubo Liang, Yiyan Ou, Xueying Liang, Huayang Zhang, You Li, Xiao Xiao, Qixia Wang, Zhengrui You, Jin Chai, M. Eric Gershwin, Ruqi Tang, Xiong Ma
Journal: Journal of Hepatology (2023)